DESCRIPTION: Many enveloped viruses have a matrix (M) protein that mediates envelopment of the nucleoprotein core (nucleocapsid) during virus assembly and budding. The M protein is putatively involved in packaging the nucleocapsid and induction of budding. The goal of this proposal is to understand how the M protein of vesicular stomatitis virus (VSV), an enveloped rhabdovirus, accomplishes these tasks. This goal will be addressed in two broad specific aims: 1. Determine the mechanism that commits intracellular M protein and nucleocapsid to virion assembly. 2. Define the role of M protein in the incorporation of viral envelope glycoprotein into virions. Specifically, M protein from virions and from infected cells will be compared for their binding affinity with nucleocapsids. These binding assays will involve minimal perturbation of nucleocapsid-M complexes assembled in vivo. Ability of M to bind with nucleocapsids will be determined in vitro. Affinity of the M protein to negative-sense versus positive-sense nucleocapsids will be determined. The M and the G protein-induced budding of membrane vesicles will be compared with virion budding, particularly in relation to the incorporation of cellular proteins. These studies are expected to provide a clearer picture of the mechanisms that underlie two critical functions of the M protein in virus assembly, e.g., packaging of the nucleocapsid and assembly of the virus envelope.